ABSTRACT
CONTENTS 12.1 Introduction 296 12.2Anatomy and Physiology of the Nervous System297
12.2.1Cellular Components of the Nervous System297 12.2.2 Central Nervous System 298 12.2.3Peripheral Nervous System298
12.3Neural Injuries 299 12.3.1CNS Trauma299 12.3.2Peripheral Nerve Injury301
12.4Clinical Challenges and Opportunities 302 12.4.1Glial Scar 304 12.4.2Myelin/Oligodendrocyte Inhibitory Molecules 304 12.4.3Blood-Brain Barrier and Blood-Spinal Cord Barrier 304 12.4.4Inšammation 305
12.5Neural Regeneration Approaches 305 12.5.1Regenerative Medicine307
12.5.1.1Drug Delivery308 12.5.1.2Plasticity Modulation 309 12.5.1.3Cell Transplantation 310 12.5.1.4Tissue Engineering and Biomaterial Strategies 312
12.5.2Neurorehabilitation 315 12.5.3Neural Prostheses316
12.5.3.1Functional Electrical Stimulation 316 12.6Future Outlook: Opportunities and Challenges 317 12.7Summary318 Acknowledgment319 References319
296
12.1 INTRODUCTION Neural regeneration following a disorder or injury to an adult mammalian nervous system is a complex biological phenomenon. During the last two decades, strategies for neural repair, functional replacement, and regeneration have included neuroprosthetic devices (Wickelgren 2004, Abbott 2006, Scott 2008), pharmacological treatments (Chau et al. 1998, Antri et al. 2003, Landry et al. 2006), stem cell-based therapies (Bareyre 2008, Coutts and Keirstead 2008), tissue-engineering approaches (Bellamkonda 2006, Kim et al. 2008, Clements et al. 2009, Orive et al. 2009), advanced neurorehabilitation (Chau et al. 1998, De Leon et al. 1999, Tillakaratne et al. 2002, Ichiyama et al. 2008), and neurobiological interventions that modulate plasticity and potentially promote neuroprotection. However, in spite of profound advances in the bioengineering strategies and in molecular-scale understanding of neural pathologies, currently no eŽective long-term treatment is available to restore complete function for a host of neural pathologies including spinal cord injury (SCI), peripheral nerve injury (PNI), stroke, traumatic brain injury (TBI), Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and multiple sclerosis (MS). Even though no single strategy has yet restored complete function a§er a neural pathology, neurobiologists, tissue engineers, and neuroprosthetists are optimistic that eŽective clinical therapies are within reach, if combinatorial therapies aimed at targeting multiple factors are implemented synergistically. …is chapter represents an exploration of the hypotheses that a speci‡c combination of biomaterial, pharmacological, cell replacement, drug delivery, and electrical stimulation, together with plasticity-promoting and neurorehabilitation-locomotor training, may interact synergistically to activate and enable functional circuits. While these disciplines have very diŽerent approaches to tackle the problem, the critical issue is-how can these diverse solutions be implemented in a manner that they are convergent, synergistic, and complementary rather than antagonistic? In this chapter, we will try to highlight convergent themes among currently parallel ‡elds of Rehabilitation, Regenerative Medicine, and Neural Prosthetics so that they can synergistically achieve the common goal of restoring function a§er neural damage.
